Oxidative Stress and Mitochondrial Complex I Dysfunction Correlate with Neurodegeneration in an α-Synucleinopathy Animal Model.
Int J Mol Sci
; 23(19)2022 Sep 27.
Article
en En
| MEDLINE
| ID: mdl-36232716
ABSTRACT
The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson's disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic ß-sitosterol ß-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy (Substantia nigra pars compacta, the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Estrés Oxidativo
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Complejo I de Transporte de Electrón
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Alfa-Sinucleína
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Sinucleinopatías
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Mitocondrias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2022
Tipo del documento:
Article